Abstract Number: Esoc2026a2147 New Insights Into the Genetic Determinants of Cervical Artery Dissection by Leveraging Large Biobanks

Abstract Background and aims Cervical artery dissection (CeAD) is a leading cause of ischemic stroke in young adults. The first and only genome-wide association study (GWAS) of CeAD was conducted in 2015 (n = 1,393/14,416). Here, we aimed to explore the genetic determinants of CeAD by conducting a new CeAD GWAS leveraging large biobanks. Methods We leveraged data from four biobanks (All of Us, Million Veteran Program, UK Biobank and FinnGen). CeAD was defined using the following ICD-10 codes: I77.71 and I77.74. We conducted a GWAS in these biobanks and meta-analyzed results with the first CeAD GWAS (n = 2,287/22,982). We performed single-variant look-ups and genetic correlation analyses with known CeAD-related traits. Finally, we performed a multi-trait GWAS (MTAG), leveraging the pairwise genetic correlation of CeAD with fibromuscular dysplasia (FMD) and spontaneous coronary artery dissection (sCAD). Results Our CeAD GWAS meta-analysis identified three genome-wide significant loci (PHACTR1,LRP1,ZBBX). Of these, LRP1 and PHACTR1 were already identified in the previous GWAS, with PHACTR1 being the only locus previously replicated. In single-variant look-ups, these two loci were associated with several traits, including sCAD, FMD and migraine. We showed significant (P 0.05) genetic correlations between CeAD and blood pressure, sCAD, intracranial aneurysms and stroke (rg = 0.38,0.59,0.38,0.34, respectively). MTAG analyses with FMD and sCAD identified four novel genome-wide significant loci requiring further investigation. Conclusions In conclusion, by leveraging large biobanks, our results provide new insights into the genetic determinants of CeAD, confirming previously identified loci and pointing to novel pathways. Further research is needed to confirm these findings and decipher the underlying biological mechanisms. Conflict of interest Quentin Le Grand, Aniket Mishra and Stéphanie Debette acknowledge support from the Fondation pour la Recherche sur les AVC; Shufan Huo: nothing to disclose; Aleksi Kristian Winstén: nothing to disclose; Teemu Niiranen: nothing to disclose; Guido Falcone: nothing to disclose; Jennifer Huffman: nothing to disclose.